Trauma-focused psychotherapies are first-line treatments for posttraumatic stress disorder (PTSD). For veterans, however, response rates are low, and dropout tends to be high. Some evidence suggests that those with comor...Trauma-focused psychotherapies are first-line treatments for posttraumatic stress disorder (PTSD). For veterans, however, response rates are low, and dropout tends to be high. Some evidence suggests that those with comorbid depression are less likely to complete treatment and improve less in trauma-focused treatments. This study examined treatment noncompletion and PTSD symptom outcomes among veterans with and without comorbid major depressive disorder (MDD) treated for PTSD with either a trauma-focused psychotherapy (prolonged exposure [PE]) or a non-trauma-focused psychotherapy (interpersonal psychotherapy [IPT]). We also examined depressive symptoms as an outcome. We conducted a secondary analysis of data from a randomized controlled trial comparing PE and IPT for the treatment of PTSD in veterans. Among 109 veterans starting treatment, 30 (52%) of 58 IPT patients and 21 (41%) of 51 PE patients were diagnosed with MDD. Those completing fewer than 8 sessions were considered noncompleters. Outcomes within each treatment and between treatments were compared by MDD status. There were no differences in noncompletion by MDD status in IPT. In PE, failure to complete was numerically but nonsignificantly higher in those without MDD. MDD was associated with significantly less PTSD symptom improvement in PE (=.04) but not in IPT at the end of treatment. Findings from a linear model incorporating posttreatment follow-up data, although not statistically significant, were consistent with the end-of-treatment findings. Comparisons between treatments among those with MDD showed partial support for an advantage of IPT for PTSD symptom improvement. There were no differences between the treatments in change in symptoms of depression. Findings are consistent with prior research showing that depression is associated with less PTSD symptom improvement in PE, a trauma-focused psychotherapy, but does not affect PTSD outcome in IPT. Although in need of replication in studies designed and statistically powered to test the role of MDD in PTSD treatment outcome, findings suggest a possible advantage for IPT relative to trauma-focused treatment for PTSD for those with comorbid MDD. ClinicalTrials.gov identifier: NCTO2586064.
Obesity and psychiatric disorders are major contributors to morbidity and premature mortality in the US and frequently co-occur, yet their joint mortality burden has not been systematically quantified nationally. We con...Obesity and psychiatric disorders are major contributors to morbidity and premature mortality in the US and frequently co-occur, yet their joint mortality burden has not been systematically quantified nationally. We conducted a retrospective population-based study of adults aged ≥25 years using the CDC WONDER Multiple Cause of Death database (1999-2023). Deaths were identified using codes for obesity (E66) and psychiatric disorders (F01-F99). Age-adjusted mortality rates (AAMRs) were calculated, and trends were assessed using joinpoint regression to estimate annual percent change (APC). Future trends through 2030 were forecasted using autoregressive integrated moving average (ARIMA) modeling. Sociodemographic and geographic disparities were examined using multivariable Poisson regression, reporting incidence rate ratios (IRRs). A total of 195,180 deaths were identified. AAMRs increased from 6.0 to 82.2 per million between 1999-2021, then declined to 66.6 per million in 2023. The steepest increases occurred in 1999-2005 (APC=+19.2%) and 2018-2021 (APC=+20.6%). Substance use disorders showed the highest burden (AAMR=29.8), followed by mood (2.6), organic (2.2), and psychotic (1.0) disorders. Mortality was higher in males (IRR=1.41) and adults aged 65-74 years (IRR=8.34). Per-capita mortality was highest among American Indian/Alaska Native populations and lowest among Asian individuals (IRR=0.09). ARIMA projected a rebound to 74.2 per million by 2030. Co-occurring obesity and psychiatric disorders are associated with rising and inequitable mortality in the US, underscoring the need for integrated obesity care, metabolic monitoring, and targeted substance use interventions.
To examine whether benzodiazepine use within 30 days after mass trauma increases posttraumatic stress disorder (PTSD) risk and whether timing or persistence of use modifies this association. This retrospective cohort st...To examine whether benzodiazepine use within 30 days after mass trauma increases posttraumatic stress disorder (PTSD) risk and whether timing or persistence of use modifies this association. This retrospective cohort study leveraged 3 advantages: large-scale clinical dataset (∼4 million individuals), unprecedented collective exposure to trauma, and novel methodological approach addressing severity bias. Using data from Clalit Health Services (covering ∼54% of the population), we identified 15,570 benzodiazepine-naïve adults who received a new benzodiazepine prescription within 30 days of index date (October 7, 2023). Medication exposure was defined by prescription redemption (none, early ≤7 days, late 8-30 days) and by persistence based on refill behavior. Incident PTSD diagnoses ( F43.1) were identified over 12 months. Cox proportional hazards models estimated hazard ratios (HRs), adjusting for demographic characteristics and psychiatric history. Overall PTSD incidence was 5.0% (773/15,570). Twelve-month risk was 5.2% for nonpurchasers, 4.7% for early purchasers, and 5.0% for late purchasers. Fully adjusted models showed no increased risk with early (HR=0.98, 95% CI=0.80-1.20) or late (HR=1.11, 95% CI=0.94-1.31) purchase. Persistent users had elevated risk (HR=1.60, 95% CI=1.14-2.25 and HR=2.07, 95% CI=1.60-2.68), whereas discontinued users did not. Among Gaza border residents (n=238), both early (HR=0.52, 95% CI=0.31-0.88) and late (HR=0.62, 95% CI=0.38-0.98) purchasers had lower PTSD risk than nonpurchasers. In this naturalistic setting of mass trauma, short-term benzodiazepine use during 30 days postexposure was not associated with increased 12 month PTSD risk. Among highly trauma-exposed individuals, it was linked to reduced risk at 12 months. These findings challenge current caution against early benzodiazepine use in the immediate aftermath of trauma.
To examine county-level variations in and correlates of substance use disorders (SUDs) health service utilization by insurance payers (Medicaid, private insurance, and Medicare) and self-pay. Service utilization (the nu...To examine county-level variations in and correlates of substance use disorders (SUDs) health service utilization by insurance payers (Medicaid, private insurance, and Medicare) and self-pay. Service utilization (the number of health care encounters, visits, admissions, or prescriptions) for SUDs was extracted from the Disease Expenditure 2017-2019 Project. We linked county-level data to drug overdose mortality rates and County Health Rankings, Area Health Resources Files, and Opioid Environment Policy Scan datasets. Descriptive and regression analyses were applied. During 2017-2019, Medicaid (52.7%) and private insurance (32.3%) financed 85.0% of annual average SUD service expenditures examined, accounting for 50.6% of SUD service utilizations (in number). Across 3,143 counties, the average annual county-level number of SUD service utilizations was 5.2 (95% CI =5.1-5.3) per 1,000 county residents. Self-pay individuals had the highest average county-level number of SUD service utilizations (8.6, 95% CI =8.4-8.6 per 1,000 county residents), followed by Medicaid beneficiaries (6.9, 95% CI =6.6-7.1 per 1,000 county Medicaid enrollees) and those paid by private insurance (2.8, 95% CI =2.7-2.8 per 1,000 privately insured county residents). County-level percentage of uninsured adults was negatively associated with SUD service utilization overall (standardized β = -.45, the highest across examined variables, <.0001), accounting for 23.0% of its variance. SUD-related health care resource indicators explained 2.3%. Across all examined payers, Medicaid funded a disproportionate share-over 50%-of SUD service expenditures. Findings quantified the substantial impact of county-level adult uninsured rates on SUD health service utilization, highlighting the pivotal role of health insurance in supporting access to and utilization of SUD services.
J Clin Psychiatry
· 2026 Jun · PMID 42283542
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Current drug policy debates often center on whether hallucinogen-related hospital admissions indicate a causal relationship with psychosis. This study examines the extent to which observed associations between hallucinog...Current drug policy debates often center on whether hallucinogen-related hospital admissions indicate a causal relationship with psychosis. This study examines the extent to which observed associations between hallucinogen use and psychosis are mediated by preexisting psychiatric conditions, providing important evidence for psychedelic policy formulation. We conducted a retrospective analysis using MarketScan Medicaid and commercial claims databases from 2015-2019. The population-based sample included individuals receiving substance use disorder treatment with documented substance-related emergency admissions or hospitalizations. We compared psychosis-related admissions occurring 30 days to 6 months postindex event between individuals with hallucinogen-related admissions versus those with nonhallucinogen substance-related admissions. Cox regression models adjusted for demographics and clinical characteristics to determine whether prior psychiatric history explained observed associations. Among 273,466 individuals with substance-related admissions, psychosis diagnoses were more prevalent following hallucinogen-related admissions (16.4%) compared to nonhallucinogen substance admissions (6.6%, <.001). While unadjusted models showed increased psychosis risk for hallucinogen-related admissions (hazard ratio [HR]=1.22, 95% CI=1.19-1.25), this association became nonsignificant after adjusting for clinical characteristics (HR=0.97, 95% CI=0.95-1.00). Apparent associations between hallucinogen use and psychosis appear largely attributable to baseline psychiatric comorbidities rather than direct causal effects. These findings carry implications for evidence-based policy development, suggesting that observed epidemiologic associations may reflect underlying vulnerability factors rather than hallucinogen-induced psychosis. Policymakers should consider these results when interpreting population-level data regarding hallucinogen safety profiles and regulatory frameworks.
The placebo effect is established in psychiatry, yet its role in substance use disorders (SUDs) treatment remains unclear. The aim of this study was to evaluate changes in craving scores in placebo groups in randomized c...The placebo effect is established in psychiatry, yet its role in substance use disorders (SUDs) treatment remains unclear. The aim of this study was to evaluate changes in craving scores in placebo groups in randomized controlled trials (RCTs) across different SUDs in adults. Eight different databases (PubMed, Embase, Web of Science, Cochrane Library, Emcare, MEDLINE, PsycINFO, and Academic Search) were systematically searched up to October 28, 2024, by 2 independent researchers. Placebo-controlled, double-blind RCTs assessing craving in patients with SUDs were included based on predefined eligibility criteria, published in English, Dutch, Spanish, or German language. Search terms were a combination and synonyms of "craving," "addiction," and "placebo." From a total of 1945 unique records identified, 9 articles met our eligibility criteria. Data on demographic characteristics, study design, and outcome results were extracted. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated for pre-post craving scores within each placebo group; a positive difference point towards improvement in the postplacebo period. A total of n=495 placebo-treated participants were included from nine RCTs in three different SUDs (n=300 in alcohol, n=88 in cocaine, and n=107 in methamphetamine use disorder). Craving scores significantly decreased over time (meaning symptom improvement) in the placebo treatment group in alcohol use disorder (5 studies, SMD=0.93 [95% CI=0.33 to 1.54]) but did not reach statistical significance in cocaine use disorder (2 studies, SMD=0.61 [95% CI=-1.41 to 2.62]) or in (meth)amphetamine use disorder (2 studies, SMD=0.44 [95% CI=-3.43 to 4.32]). Placebo treatment led to reductions in craving scores across all three SUDs, although statistical significance was achieved only in alcohol use disorder. Given the low number of studies for cocaine and (meth)amphetamine use disorder, these estimates were captured with much uncertainty. These findings may inform the design of future RCTs and support the development of more individualized treatment approaches in clinical settings.
Postpartum depression (PPD) is a debilitating mood disorder with peripartum onset. Current treatment options are limited in PPD. GH001 is a synthetic inhalation formulation of the psychoactive molecule mebufotenin (5-MeO...Postpartum depression (PPD) is a debilitating mood disorder with peripartum onset. Current treatment options are limited in PPD. GH001 is a synthetic inhalation formulation of the psychoactive molecule mebufotenin (5-MeO-DMT). This trial investigated the preliminary efficacy and safety of GH001 in adult females with PPD. This phase 2a, proof-of-concept, open-label trial enrolled women aged 18-45 years (March 2023 to August 2024) with a Mini-International Neuropsychiatric Interview-confirmed diagnosis of major depressive disorder with peripartum onset. Patients had Montgomery-Asberg Depression Rating Scale (MADRS) scores of ≥28 at baseline. GH001 was administered as an individualized dosing regimen of up to 3 escalating doses (6, 12, and 18 mg) on day 1. The primary end point was the change in MADRS total score from baseline to day 8. Secondary end points included antidepressant response (≥50% reduction), remission (MADRS total score ≤10), and safety and tolerability of GH001. Ten patients were enrolled. Mean baseline MADRS total score was 36.7 (SD = 4.8). Mean MADRS total score change from baseline to day 8 was -35.4 points (SD = 5.5; < .0001). All patients achieved response and were in remission on day 8, which was first observed 2 hours after their final dose on day 1. Inhalation of GH001 was well tolerated, and no serious adverse events (AEs) were reported. All treatment-emergent AEs were mild or moderate, with headache as the most frequently reported AE. GH001 demonstrated rapid and significant improvements in depressive symptoms and remission of PPD with an acceptable safety profile and parallel improvements across secondary end points. ClinicalTrials.gov identifier: NCT05804708; EudraCT identifier: 2021-006879-42.
Sleep is an important biological function. This article considers practical matters related to the prescription of sedative-hypnotic drugs to patients with insomnia. This article also presents practical suggestions for t...Sleep is an important biological function. This article considers practical matters related to the prescription of sedative-hypnotic drugs to patients with insomnia. This article also presents practical suggestions for the management of excessive sedation in patients who need pharmacologic treatments with sedating adverse effects when dose reduction is not an option. Issues examined include the choice of drug for sleep-onset insomnia and for sleep-maintenance insomnia; the choice of drug for insomnia in patients with psychiatric disorders; sedative-hypnotic dosing in contexts such as perturbation of multiple neurotransmitter systems; metabolic drug interactions with sedative-hypnotic drugs; gastrointestinal absorption of hypnotic drugs and time to onset of drowsiness; the effect of food on absorption and time to onset of drowsiness; the effect of glucagon-like peptide-1 receptor agonist (GLP-1RA) drugs on absorption and time to onset of drowsiness; the importance of half-life for the duration of action of the sedative-hypnotic drug; strategies to address oversedation with sedating psychotropic drugs; treating insomnia with classical monoamine oxidase inhibitors, especially tranylcypromine; optimization of sedative-hypnotic therapy; provision of patient guidance; and related matters. Readers are also reminded that sleep hygiene and cognitive-behavioral approaches should routinely be combined with sedative-hypnotic drug therapy to optimize insomnia care and improve treatment outcomes.
Posttraumatic stress disorder (PTSD) is a prevalent and disabling condition among US military veterans. Prior waves of the National Health and Resilience in Veterans Study (NHRVS; 2011-2020) have estimated the lifetime a...Posttraumatic stress disorder (PTSD) is a prevalent and disabling condition among US military veterans. Prior waves of the National Health and Resilience in Veterans Study (NHRVS; 2011-2020) have estimated the lifetime and past-month prevalence of PTSD at 8.0%-9.4% and 4.7%-5.0%, respectively. Updated national surveillance data are needed given demographic changes in the veteran population and evolving patterns of trauma exposure. Data were drawn from the 2025-2026 NHRVS, a nationally representative, web-based survey of 2,636 US veterans. Weighted prevalence estimates of lifetime and past-month PTSD were compared with estimates from prior NHRVS waves (2011, 2013, and 2019-2020). Linear regression assessed associations among trauma burden, PTSD, and functional disability. In 2025-2026, the weighted prevalence of lifetime PTSD was 14.4% (95% CI, 12.6%-16.4%), and the prevalence of past-month PTSD was 7.3% (95% CI, 6.0%-8.9%), both significantly higher than those observed in prior NHRVS waves. Compared with 2019-2020, the prevalence of past-month PTSD was higher among men, white and racial/ethnic minority veterans, and veterans aged 18-59 years. Sudden loss, life-threatening illness or injury, and witnessed violence were the most frequently identified index traumas, whereas forced sexual experiences were associated with the highest conditional risk of PTSD. Greater cumulative trauma burden and PTSD were each strongly associated with increased functional disability. PTSD affects a substantial and growing proportion of US veterans. Cumulative trauma burden and PTSD are strongly associated with functional disability, underscoring the importance of assessing lifetime trauma exposure alongside PTSD symptoms in clinical care and population surveillance.
Adult attention-deficit/hyperactivity disorder (ADHD) is commonly associated with comorbidities, including depression and anxiety; however, most ADHD treatment studies exclude people with these conditions. This phase 4,...Adult attention-deficit/hyperactivity disorder (ADHD) is commonly associated with comorbidities, including depression and anxiety; however, most ADHD treatment studies exclude people with these conditions. This phase 4, open-label, decentralized clinical trial (conducted March 25, 2024-December 11, 2024) evaluated viloxazine ER (extended-release capsules, an FDA-approved nonstimulant medication for ADHD) in adults with ADHD (based on ) and comorbid depression and/or anxiety symptoms. Participants received viloxazine ER (200-600 mg/d) for 14 weeks added to existing medications (including stimulant, antidepressant, or anxiolytic medications). Efficacy and safety measures (assessed via televisit, mobile phone app, and home monitoring devices) included clinician-and patient-reported scales evaluating ADHD, depression, and anxiety symptoms, treatment-emergent adverse events, blood pressure, pulse rate, weight, and suicidality assessment. The primary end point was change from baseline in Adult ADHD Investigator Symptom Rating Scale (AISRS) total score. Among participants receiving viloxazine ER (n=161; mean age, 39.4 years; female, 75.8%), almost all (99.4%) had substantial depression and anxiety symptoms. AISRS total score was significantly reduced (improved) from baseline (mean [SD], 37.5 [6.53]; n=150) at week 14/end of study (EOS) (mean [SD] change, -17.3 [11.34]; <.0001); similar results were observed for patient-reported ADHD symptoms. Depression and anxiety rating scales were significantly improved from baseline to week 14/EOS (all <.0001). Safety outcomes were consistent with previous viloxazine ER studies; 24 participants (14.9%) had adverse events leading to study discontinuation. Viloxazine ER was well tolerated and associated with improvements in ADHD, depression, and anxiety symptoms in this real-world study of adults with ADHD and comorbid symptoms. ClinicalTrials.gov identifier: NCT06185985.
Nonsuicidal self-injury (NSSI) refers to deliberate, repeated acts of damaging one's own body tissue without suicidal intent. The aim of this systematic review and meta-analysis was to explore the effectiveness of mood s...Nonsuicidal self-injury (NSSI) refers to deliberate, repeated acts of damaging one's own body tissue without suicidal intent. The aim of this systematic review and meta-analysis was to explore the effectiveness of mood stabilizers in treating depressive adolescent patients with NSSI in China. Literature published before June 30, 2025, was included. Chinese databases searched included CBM (Chinese Biomedical Database), CNKI (China National Knowledge Infrastructure), WANFANG (Wanfang Database), and CSSCI (Chinese Social Sciences Citation Index); English databases included MEDLINE, Embase, and the Cochrane Library. Searches used the following keywords: [Bipolar disorder OR depression OR NSSI] AND [Mood stabilizer OR Lithium OR Valproate OR Carbamazepine OR Oxcarbazepine OR Lamotrigine OR Antipsychotic OR Antidepressant]. Chinese and English literature related to the treatment of NSSI with mood stabilizers in adolescent patients in China was searched. Editorials, comments, letters, reviews, and case reports were excluded. Randomized controlled trials conducted in China comparing mood stabilizer augmentation of basic therapy versus basic therapy alone for treating NSSI were included, and studies evaluating mood stabilizer treatment for NSSI using pre-post designs were also included. A total of 9 studies were included, 4 comparative studies by control group and 5 comparative studies of before and after treatment. Indices of depression, anxiety, impulsivity, self-injury severity, and treatment response were synthesized and analyzed. Mean differences or standardized mean differences and 95% confidence intervals (CIs) were used for symptom change. Odds ratios and their 95% CIs were also used for binary outcomes. Severity of anxiety, depression, impulsivity, and self-injury was significantly reduced following treatment with mood stabilizers. Compared to treatment without mood stabilizers, anxiety, depression, and self-injury were also significantly reduced, and the response rate was significantly improved in adolescents with depression and NSSI. The incidence of self-injury in these patients was significantly reduced by mood stabilizers. These results demonstrate the important role of mood stabilizers in treating NSSI and suggest that mood stabilization may be more critical than mere improvement of affective symptoms.
Individuals with avoidant/restrictive food intake disorder (ARFID) commonly endorse lacking interest in eating/food, difficulties recognizing hunger, and early satiation. Cholecystokinin (CCK) and ghrelin may be importan...Individuals with avoidant/restrictive food intake disorder (ARFID) commonly endorse lacking interest in eating/food, difficulties recognizing hunger, and early satiation. Cholecystokinin (CCK) and ghrelin may be important biologic mechanisms in ARFID given their role in appetite signaling. We investigated whether youth with ARFID- had greater CCK and lower ghrelin levels compared to youth without this presentation across timepoints and whether greater reductions in CCK and increases in ghrelin were associated with ARFID symptom improvement over a two-year period. One hundred youth (49% female, mean [SD] age=15.87 [3.89] years, mean [SD] body mass index percentile=37.71 [35.16]) recruited from a single-center clinic and surrounding community, initially meeting criteria for full/subthreshold ARFID completed the Pica, ARFID, and Rumination Disorder Interview at baseline and follow-up over two years (July 2016-September 2022) to determine ARFID diagnosis, presentation type, and severity scores. We obtained fasting plasma levels of CCK and ghrelin at each timepoint. Youth with ARFID- had higher CCK than those without this presentation, though there were no differences in fasting ghrelin. Greater decreases in CCK from Baseline to Years 1 and 2 were associated with decreases in lack of interest severity at Years 1 and 2, whereas greater increases in ghrelin from Baseline to Years 1 and 2 were associated with decreases in ARFID severity at Years 1 and 2. In the first longitudinal study of neuroendocrine abnormalities in individuals with ARFID, we found that decreases in CCK and increases in ghrelin were associated with improvements in ARFID symptomology.
Aftercare interventions following self-harm may prevent subsequent self-harm and suicide deaths. However, previous research into the effectiveness of aftercare services on self-harm repetition and suicide mostly comprise...Aftercare interventions following self-harm may prevent subsequent self-harm and suicide deaths. However, previous research into the effectiveness of aftercare services on self-harm repetition and suicide mostly comprised a small sample size and showed inconsistent findings. We investigated the effectiveness of Taiwan's national self-harm aftercare program on self-harm repetition and suicide among self-harm patients. A cohort study of 90,413 index self-harm episodes (ie, the first episode during the study period) presented to hospitals and registered in the National Suicide Surveillance System (2012-2016) was performed. Cox regression models were used to evaluate the risk of self-harm repetition or suicide after receiving the aftercare, which was modeled as a time-varying variable. The aftercare was associated with a 17% (adjusted hazard ratio [aHR]=1.17, 95% confidence interval [CI] 1.14-1.21) increase in self-harm repetition risk and a 20% (aHR=0.80, 95% CI 0.74-0.86) decrease in suicide risk. The association of the aftercare with increased self-harm repetition risk was most marked in patients aged 45-64 years (aHR=1.34) and more marked in those with a history of psychiatric disorders (aHR=1.26). The association of aftercare with decreased suicide risk was most marked in patients aged 10-24 years (aHR=0.64) and more marked in those without a history of psychiatric disorders (aHR=0.76) than their counterparts. The aftercare following self-harm was associated with an increased risk of repeat self-harm hospital presentation and decreased risk of suicide. The findings suggest that the aftercare intervention may increase help-seeking behaviors after self-harm and decrease suicide deaths, especially in specific subgroups.
Negative symptoms remain among the most debilitating and treatment-resistant features of schizophrenia. Repetitive transcranial magnetic stimulation, particularly intermittent theta burst stimulation (iTBS), is emerging...Negative symptoms remain among the most debilitating and treatment-resistant features of schizophrenia. Repetitive transcranial magnetic stimulation, particularly intermittent theta burst stimulation (iTBS), is emerging as a promising intervention targeting these domains. This study aimed to evaluate the efficacy of experimental iTBS applied to the left dorsolateral prefrontal cortex (DLPFC) in ameliorating negative symptoms in patients with schizophrenia. In a double-blind, randomized, sham-controlled design, patients with schizophrenia (active group = 71) received daily sessions of experimental iTBS or sham stimulation (sham group = 70) over the left DLPFC for 3 weeks. Clinical outcomes were assessed using the Scale for the Assessment of Negative Symptoms, with a focus on the negative subscale. Patients were diagnosed based on clinical criteria. Compared to sham, active experimental iTBS did not result in statistically significant improvements in negative symptoms at posttreatment or follow-up. However, the results indicate that experimental iTBS is a safe and well-tolerated intervention with minor adverse effects. Consistent with several recent large-scale trials and meta-analyses, the findings suggest limited efficacy of experimental iTBS over the left DLPFC for negative symptoms. Future research may investigate alternative stimulation targets, protocols, or combined interventions to enhance treatment outcomes in this population. Clinical Trial Registry-India (CTRI) identifier: CTRI/2019/05 019099.
To evaluate the efficacy, safety, and durability of a single 25-mg dose of a proprietary, synthetic formulation of psilocybin with psychological support for reducing chronic suicidal ideation in a treatment-resistant pop...To evaluate the efficacy, safety, and durability of a single 25-mg dose of a proprietary, synthetic formulation of psilocybin with psychological support for reducing chronic suicidal ideation in a treatment-resistant population. This was an open-label, single-arm study with a 12-week follow-up conducted between March 2022 and May 2025. Twenty adults with chronic suicidal ideation, major depressive disorder (), and ≥2 prior antidepressant treatment failures received a single 25-mg dose of psilocybin administered within a structured preparatory and integration psychotherapy protocol. The primary outcome was change from baseline in the Modified Scale for Suicidal Ideation (MSSI) at week 3. Secondary outcomes included change in MSSI at weeks 1 and 12 and change in Montgomery-Asberg Depression Rating Scale (MADRS) scores at weeks 1, 3, and 12. Outcomes were analyzed using 1-way repeated-measures analysis of variance with Bonferroni-adjusted pairwise comparisons. Significant reductions in MSSI scores were observed from baseline to week 3 (primary end point: mean difference [MD] = 13.95; 95% CI, 8.63-19.27; < .001; = 1.73). Improvements were rapid and durable, with significant reductions at week 1 (MD = 15.10; < .001; = 2.11) and week 12 (MD = 13.00; < .001; = 1.46). By week 12, 70% (n=14) of participants achieved MSSI ≤2. MADRS scores showed similar significant reductions at all postbaseline time points (MD range: 17.55-20.50; all < .001; = 1.63-1.97). No serious adverse events occurred. In this open-label single-arm study of adults with chronic suicidal ideation and prior treatment failures, a single administration of psilocybin with psychological support was associated with rapid, large-magnitude, and durable reductions in suicidal ideation and depressive symptoms through 12 weeks. These preliminary findings support further evaluation in larger randomized controlled trials. ClinicalTrials.gov Identifier: NCT05220410.